Human immunodeficiency virus (HIV) infects a cell expressing a CD4 molecule (e.g., a T cell) to destroy the cell. Therefore, the number of CD4-positive T cells (helper T cells) is decreased and the cellular immunity is lowered in a human body infected with HIV. The infection finally leads to severe immunodeficiency conditions, resulting in onset of an opportunistic infection such as carinii pneumonia. The conditions are called acquired immunodeficiency syndrome (AIDS).
As to methods for treating HIV infection, antiviral agents that block the life cycle of the HIV (reverse transcriptase inhibitors, protease inhibitors, etc.) and vaccines have been developed, and several antiviral agents have been put to practical use. However, since the mutation frequency in the HIV is high, a mutant against which the above-mentioned agents are not effective may emerge in an infected individual. Thus, it cannot be necessarily said that a specific remedy has been completed. In another approach, attempts to develop gene therapy drugs using nucleic acids (an RNA decoy, a ribozyme, etc.) or proteins (transdominant mutant proteins, intracellular antibodies, etc.) as effective ingredients to inhibit the multiplication of HIV have not attained the stage of completion.
A method in which cell death is caused specifically in a cell infected with HIV has been devised (e.g., Patent Document 1, Non-patent Documents 1, 2 and 3). According to such a method, a gene encoding a product that exhibits cytotoxicity is connected downstream of an LTR promoter from HIV. To date, there has been no known case where the method is clinically applied. Use of a ribonuclease as the product that exhibits cytotoxicity is described in Patent Document 2 (U.S. Pat. No. 5,837,510), although death of HIV-infected cells caused by the ribonuclease has not been confirmed. It is known that human pancreatic ribonuclease (RNase 1), which is representative ribonuclease, is inhibited by a ribonuclease inhibitor in cytoplasm (Non-patent Document 4). Thus, it cannot be said that it is suitable for the above-mentioned purpose.
It has been reported that several prokaryotic plasmids have a post-segregation killing (PSK) function to kill hosts from which the plasmids have been dropped out in order to maintain the plasmids in the hosts. Such plasmids have toxin-antitoxin genes. An antitoxin binds to a toxin in a cell to inactivate the toxin. The antitoxin is labile to degradation by proteases. Degradation of the antitoxin by proteases results in activation of the toxin which is stable. Such toxin-antitoxin genes also exist on chromosomes of most prokaryotes. They respond to various stresses and have functions in programmed cell death. Although the functions of the toxins have not been fully proven, it is known that both MazF, which is a toxin of the mazE-mazF system (Non-patent Document 5), and PemK, which is a toxin of the pemI-pemK system (Non-patent Document 6), have sequence-specific ribonuclease activities. Furthermore, a method for obtaining a highly pure protein of interest has been proposed (Patent Document 3). In this method, mRNA is degraded utilizing such a toxin, and only an mRNA encoding the protein of interest from which the sequences cleaved by the toxin have been eliminated beforehand is translated.    Patent Document 1: U.S. Pat. No. 5,554,528    Patent Document 2: U.S. Pat. No. 5,837,510    Patent Document 3: WO 2004/113498    Non-patent Document 1: Hum. Gene Therapy, 2: 53-61 (1991)    Non-patent Document 2: Proc. Natl. Acad. Sci. USA, 91:365-369 (1994)    Non-patent Document 3: Hum. Gene Therapy, 10:103-112 (1999)    Non-patent Document 4: Proc. Natl. Acad. Sci. USA, 95:10407-10412 (1998)    Non-patent Document 5: Molecular Cell, 12:913-920 (2003)    Non-patent Document 6: J. Biol. Chem., 279:20678-20684 (2004)